In a recent study published in the journal PNAS, investigators have discovered a two-pronged therapeutic approach that shows great potential for weakening and then defeating cancer cells. The research team’s mix of genetic and biochemical experiments uncovered a avenue to enhance the presence of a tumor-suppressing protein, which stimulates cancer cells for self-destruction.
The finding holds the promise of increasing the effectiveness of radiation and chemotherapy in killing cancer if the research is supported by tests in animal models. The key is to increase p53-binding protein 1 (53BP1) so that it can weakens the cancer cells, leaving them more susceptible to existing cancer-fighting treatments.
New discovery for treating cancer
Researchers insisted on that the discovery could lead to a gene therapy where extra amount of 53BP1 will be generated to make cancer cells more susceptible to cancer measures. Alternatively, they could design other molecules to enhance levels of 53BP1 in cancer with the same cancer-killing effect.
The basis of the research involves DNA repair -more specifically, double-strand DNA repair. DNA damage is the consequence of an irregular change in the chemical structure of DNA, in which double-strand break in the chromosome is the most lethal irregularity to DNA.
There are two repair pathways operated in the body to fix these double strand breaks. One provides rapid, yet incomplete repair — namely, gluing the DNA strand ends back together. The second pathway uses information from intact, undamaged DNA to instruct damaged cells on how to mend broken double strands. During the study, investigators discovered a previously unidentified function of a known gene, UbcH7, in regulating DNA double-strand break repair. Specifically, they found that depleting UbcH7 led to a dramatic increase in the level of the 53BP1 protein.
The aim of the study is to increase the level of 53BP1 to force cancer cells into the error-prone pathway where they will die. Investigators expect to suppress deliberately the second repair pathway, the measure probably giving rise to enhanced effectiveness of cancer therapy drugs. To examine further, investigators would study the effects of introducing the protein 53BP1 in lab mice with cancer.
Reference:
UbcH7 regulates 53BP1 stability and DSB repair. Proceedings of the National Academy of Sciences, 2014; 111 (49): 17456